Regioselective Aliphatic Carbon–Carbon Bond Cleavage by a Model System of Relevance to Iron-Containing Acireductone Dioxygenase

Mononuclear Fe­(II) complexes ([(6-Ph2TPA)­Fe­(PhC­(O)­C­(R)­C­(O)­Ph)]­X
(3-X: R = OH, X = ClO4 or OTf; 4: R = H, X = ClO4)) supported by the 6-Ph2TPA
chelate ligand (6-Ph2TPA = N,N-bis­((6-phenyl-2-pyridyl)­methyl)-N-(2-pyridylmethyl)­amine)
and containing a β-diketonate ligand bound via a six-membered
chelate ring have been synthesized. The complexes have all been characterized
by 1H NMR, UV–vis, and infrared spectroscopy and
variably by elemental analysis, mass spectrometry, and X-ray crystallography.
Treatment of dry CH3CN solutions of 3-OTf with
O2 leads to oxidative cleavage of the C(1)–C(2)
and C(2)–C(3) bonds of the acireductone via a dioxygenase reaction,
leading to formation of carbon monoxide and 2 equiv of benzoic acid
as well as two other products not derived from dioxygenase reactivity:
2-oxo-2-phenylethylbenzoate and benzil. Treatment of CH3CN/H2O solutions of 3-X with O2 leads to the formation of an additional product, benzoylformic acid,
indicative of the operation of a new reaction pathway in which only
the C(1)–C(2) bond is cleaved. Mechanistic studies show that
the change in regioselectivity is due to the hydration of a vicinal
triketone intermediate in the presence of both an iron center and
water. This is the first structural and functional model of relevance
to iron-containing acireductone dioxygenase (Fe-ARD′), an enzyme
in the methionine salvage pathway that catalyzes the regiospecific
oxidation of 1,2-dihydroxy-3-oxo-(S)-methylthiopentene
to form 2-oxo-4-methylthiobutyrate. Importantly, this model system
is found to control the regioselectivity of aliphatic carbon–carbon
bond cleavage by changes involving an intermediate in the reaction
pathway, rather than by the binding mode of the substrate, as had
been proposed in studies of acireductone enzymes.